The main purpose of this investigation continues to be the definition of the extent of autonomy of the mitochondrion in its biogenesis. During the grant period our aim will be: 1) A more extended identification and complete documentation of the polypeptides synthesized by the mitochondria and a test of their function, whether participating in the catalytic process or integration into the mitochondrial membrane. 2) The determination whether such polypeptides are coded for by mitochondrial DNA, and a description of the nature and kinetics of formation of mitochondrial mRNA. 3) An investigation into the genetic capabilities of wild type (p positive) and mutant (p negative) mitochondrial DNAs, their interconversion by representatives of three classes of mutagens (ethidium bromide, berenil, euflavine) and modulating agents such as Antimycin A. Special emphasis will be placed on documenting the possible involvement of various components of the mitochondrial damage repair system and the inner membrane. Coincident with these studies we will investigate the function and interaction of these mitochondrial with other entities in the nucleus and cell sap during cellular activity, proliferation and differentiation, as well as the regulation of these processes.